Transgenic expression of the amyloid-β precursor protein-intracellular domain does not induce Alzheimer's disease-like traits in vivo

Luca Giliberto, Cristina d'Abramo, Christopher Michael Acker, Peter Davies, Luciano D'Adamio

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Regulated intramembranous proteolysis of the amyloid-β precursor protein by the γ-secretase yields amyloidβ, which is the major component of the amyloid plaques found in Alzheimer's disease (AD), and the APP intracellular domain (AID). In vitro studies have involved AID in apoptosis and gene transcription. In vivo studies, which utilize transgenic mice expressing AID in the forebrain, only support a role for AID in apoptosis but not gene transcription. Methodology/Principal Findings: Here, we have further characterized several lines of AID transgenic mice by crossing them with human Tau-bearing mice, to determine whether over-expression of AID in the forebrain provokes AD-like pathologic features in this background. We have found no evidence that AID overexpression induces AD-like characteristics, such as activation of GSK-3β, hyperphosphorylation of Tau and formation of neurofibrillary pathology. Conclusions/Significance: Overall, these data suggest that AID transgenic mice do not represent a model that reproduces the overt biochemical and anatomo-pathologic lesions observed in AD patients. They can still be a valuable tool to understand the role of AID in enhancing the cell sensitivity to apoptotic stimuli, whose pathways still need to be characterized.

Original languageEnglish (US)
Article numbere11609
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - Jul 16 2010

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Amyloid beta-Protein Precursor
amyloid
Alzheimer disease
Amyloid
Alzheimer Disease
Transgenic Mice
gene expression
mice
genetically modified organisms
Transcription
Prosencephalon
Bearings (structural)
apoptosis
proteins
transcription (genetics)
Genes
Proteolysis
Apoptosis
Glycogen Synthase Kinase 3
brain

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transgenic expression of the amyloid-β precursor protein-intracellular domain does not induce Alzheimer's disease-like traits in vivo. / Giliberto, Luca; d'Abramo, Cristina; Acker, Christopher Michael; Davies, Peter; D'Adamio, Luciano.

In: PLoS One, Vol. 5, No. 7, e11609, 16.07.2010.

Research output: Contribution to journalArticle

Giliberto, Luca ; d'Abramo, Cristina ; Acker, Christopher Michael ; Davies, Peter ; D'Adamio, Luciano. / Transgenic expression of the amyloid-β precursor protein-intracellular domain does not induce Alzheimer's disease-like traits in vivo. In: PLoS One. 2010 ; Vol. 5, No. 7.
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